6-89290835-C-T

Variant names:

• chr6-89290835-C-T
• rs9451196
• NM_002043.5:c.220+8924G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002043.5(GABRR2):​c.220+8924G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,090 control chromosomes in the GnomAD database, including 2,892 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2892 hom., cov: 32)
• Consequence: GABRR2 NM_002043.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144

Genes affected

GABRR2 (HGNC:4091): (gamma-aminobutyric acid type A receptor subunit rho2) Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA receptors, which are ligand-gated chloride channels. The protein encoded by this gene is a member of the rho subunit family and is a component of the GABA type A receptor complex. This gene exists on chromosome 6q next to the gene encoding the rho 1 subunit of the GABA type A receptor, in a region thought to be associated with susceptibility for psychiatric disorders and epilepsy. Polymorphisms in this gene may also be associated with alcohol dependence, and general cognitive ability. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR2	NM_002043.5	c.220+8924G>A		intron_variant	Intron 2 of 8	ENST00000402938.4	NP_002034.3
GABRR2	XM_047418599.1	c.295+8924G>A		intron_variant	Intron 2 of 9		XP_047274555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR2	ENST00000402938.4	c.220+8924G>A		intron_variant	Intron 2 of 8	1	NM_002043.5	ENSP00000386029.4
GABRR2	ENST00000602808.1	n.354+8924G>A		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27452 AN: 151972 Hom.: 2891 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.178

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.181 AC: 27462 AN: 152090 Hom.: 2892 Cov.: 32 AF XY: 0.184 AC XY: 13715 AN XY: 74338

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.176

Alfa AF: 0.126 Hom.: 1301

Bravo AF: 0.184

Asia WGS AF: 0.383 AC: 1329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.8
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9451196; hg19: chr6-90000554; COSMIC: COSV68766140;